Establishing Serum Thyroglobulin Reference Values and Predictors of Its Variability in an Iodine-Sufficient Population.

Objectives: Serum thyroglobulin (Tg) is a key biomarker for various thyroid conditions. However, population-specific reference values (RVs) are missing, and clinical practice relies on manufacturer-provided RVs. This study aimed to establish Tg RVs in an iodine-sufficient population using the strict National Academy of Clinical Biochemistry (NACB) criteria and to identify determinants of serum Tg levels.

Methods: We screened 420 volunteers through history, physical examination, thyroid function tests, urine iodine excretion, and thyroid ultrasonography. Thyroid volume (TTV) was estimated in a subset of the study population. We selected 140 subjects for NACB criteria-based Tg RVs determination (Cohort 1) and 154 for Tg determinant analysis (Cohort 2). Redundancy Analysis and Variation Partition were performed to quantify the explained variance of Tg from 5 variables -smoking, age, gender, thyrotropin, and TTV.

Results: The RVs for Tg, calculated as mean ± 2 standard deviations on log-transformed data (as per the NACB criteria), were 2.95-56.23 ng/mL, whereas those suggested by our Tg assay manufacturer are 3.5-77 ng/mL. A model including all 5 predictors explained only 7.5% of Tg variability, with smoking (4.8%) and TTV (2.7%) as the only significant contributors. Subgroup analysis showed that thyrotropin had a minor impact only in men, while age and gender were not significant contributors.

Conclusions: Population-specific RVs for Tg are essential in clinical decision-making. Known clinical/biochemical variables explained only a small proportion of Tg variability. Our findings underscore the need to identify additional determinants of Tg levels.